WO2009150902A1 - 外用組成物 - Google Patents

外用組成物 Download PDF

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Publication number
WO2009150902A1
WO2009150902A1 PCT/JP2009/058022 JP2009058022W WO2009150902A1 WO 2009150902 A1 WO2009150902 A1 WO 2009150902A1 JP 2009058022 W JP2009058022 W JP 2009058022W WO 2009150902 A1 WO2009150902 A1 WO 2009150902A1
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WO
WIPO (PCT)
Prior art keywords
oil
composition
component
skin
external use
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2009/058022
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
彰寛 青木
若松　康三郎
篠原　茂生
修 高須
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Otsuka Pharmaceutical Co Ltd
Original Assignee
Otsuka Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Otsuka Pharmaceutical Co Ltd filed Critical Otsuka Pharmaceutical Co Ltd
Priority to EP18150042.2A priority Critical patent/EP3335693B1/en
Priority to CN2009801009462A priority patent/CN101854911B/zh
Priority to EP09762333.4A priority patent/EP2298275B1/en
Priority to ES09762333.4T priority patent/ES2671040T3/es
Priority to US12/996,929 priority patent/US10966983B2/en
Priority to KR1020177003652A priority patent/KR101850405B1/ko
Priority to KR1020097026200A priority patent/KR101746743B1/ko
Priority to JP2009531683A priority patent/JP4403467B1/ja
Priority to CA2727272A priority patent/CA2727272A1/en
Publication of WO2009150902A1 publication Critical patent/WO2009150902A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/606—Nucleosides; Nucleotides; Nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/007—Preparations for dry skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin

Definitions

  • the present invention relates to an external composition
  • an external composition comprising an essential oil and a purine base and / or a salt thereof.
  • Examples of the skin aging phenomenon include pigmentation such as spots, freckles, and liver spots, dullness, dryness, wrinkles and the like. Preventing such skin aging is a great health and beauty concern especially for women.
  • Essential oils are known as organic compounds containing volatile aromatic substances contained in plants. In addition to its use as a perfume, essential oils are known for antibacterial and antifungal effects, periodontal disease prevention effects (see Patent Document 1), and the like. However, little is known about the effects of applying essential oils to the skin.
  • O / W type compositions containing adenine and the like are known as means for improving skin aging (see Patent Documents 2 and 3).
  • Purine bases are known to promote skin turnover by increasing intracellular ATP levels and to prevent pigmentation such as spots and liver spots.
  • IGF-1 insulin-like growth factor-1
  • purine bases are not known to promote IGF-1 secretion.
  • the skin consists of the epidermis on the surface, the dermis in the deep layer, and the subcutaneous tissue.
  • the outermost layer of the epidermis has a stratum corneum.
  • the stratum corneum created by epidermal cells is a barrier that separates the external environment from the inside of the body, and the quality of the stratum corneum is an extremely important factor that determines the freshness of the skin.
  • the stratum corneum contains intercellular lipids, natural moisturizing factor (NMF), etc., and not only prevents moisture transpiration from the inside of the skin, but also the stratum corneum itself retains moderate moisture, Maintains the softness and smoothness.
  • NMF natural moisturizing factor
  • the “stratum corneum water amount” representing the water retention ability of the stratum corneum or “transepidermal water loss (TEWL) which is the amount of water evaporated from the stratum corneum surface” Loss) "is used.
  • TEWL transepidermal water loss
  • the skin As the skin ages, the skin is characterized by atrophy of the epidermis, thickening of the stratum corneum, and disappearance of the granular layer present under the stratum corneum. Aged skin exhibiting such characteristics has a lower stratum corneum moisture content and lower TEWL than young skin. It is known that such aging skin causes the skin surface to become rough as the outside air dries, and is accompanied by shallow cracks and itching. With conventional skin creams, the amount of skin transpiration can be suppressed by protecting the stratum corneum surface, and a temporary increase in the amount of stratum corneum moisture can be expected, but the effect was immediately lost when the use was stopped.
  • the main object of the present invention is to provide a composition for external use that can enhance the secretion promoting action of IGF-1. Moreover, the composition for external use which can increase the amount of skin stratum corneum moisture and can maintain the amount of transepidermal water loss in an appropriate state is also provided.
  • the present invention provides the following external composition, method for producing the external composition, and method for promoting IGF-1 secretion in the skin.
  • Item 1 External composition containing the following component (A) and component (B): (A) essential oil; (B) At least one selected from the group consisting of purine bases and salts thereof.
  • the component (A) is at least one essential oil selected from the group consisting of Daiki Oyster Oil, Ohihiba Oil, Atlas Cider Oil, Labandula Hybrida Oil, Lime Oil, Pepper Oil, Scots Pine Oil, Rosemary Oil and Turpentine Oil Item 2.
  • composition for external use according to Item 1 or 2 wherein the component (A) is at least one essential oil selected from the group consisting of Daiki Oka oil, Scots pine oil and Labandula hybrida oil.
  • Item 4. The composition for external use according to any one of Items 1 to 3, wherein the component (A) is an essential oil comprising a mixture of Daiki Oka oil, Scots pine oil and Labandula hybrida oil.
  • Item 5. is an essential oil comprising a mixture of Daiwyo Oil, Ohihiba Oil, Atlas Cider Oil, Labandula Hybrida Oil, Lime Oil, Pepper Oil, Red Pine Oil, Rosemary Oil and Turpentine Oil The external composition in any one.
  • Item 6. Item 6.
  • Item 7. The composition for external use according to any one of Items 1 to 6, wherein the component (B) is adenosine 5′-monophosphate or a salt thereof.
  • Item 8. The composition for external use according to any one of Items 1 to 7, wherein the proportion of component (A) is 0.00001 to 40% by weight.
  • Item 9. Item 9. The composition for external use according to any one of Items 1 to 8, wherein the blending ratio of the component (B) is 0.01 to 20% by weight.
  • Item 10. Item 10.
  • Item 11. The composition for external use according to any one of Items 1 to 10, which is for promoting IGF-1 secretion in the skin.
  • Item 12. The composition for external use according to any one of Items 1 to 10, which is used to increase the amount of stratum corneum moisture in the skin.
  • Item 14. Item 14.
  • composition for external use according to any one of Items 1 to 13, which is in the form of cosmetics or quasi drugs.
  • Item 15. The following (A) component and (B) component (A) essential oil; (B) A method for producing an external composition for promoting IGF-1 secretion, comprising at least one selected from the group consisting of purine bases and salts thereof.
  • Item 16. Use of the following components (A) and (B) for producing a composition for promoting IGF-1 secretion in the skin: (A) essential oil; (B) At least one selected from the group consisting of purine bases and salts thereof.
  • Item 19 An external composition containing capsaicin and at least one selected from the group consisting of purine bases and salts thereof.
  • the capsaicin is selected from the group consisting of capsaicin ((6E) -N-[(4-Hydroxy-3-methoxyphenyl) methyl] -8-methylnon-6-enamide), nonyl acid vanillylamide (N-Vanillylnonanamide) and dihydrocapsiate Item 20.
  • composition for external use of the present invention synergistically enhances the IGF-1 production-promoting action of essential oil by using a combination of essential oil and purine base and / or salt thereof, and remarkably promotes IGF-1 secretion in the skin.
  • the composition for external use of the present invention has the effects of reducing pigmentation (decreasing melanin amount), increasing skin lightness (preventing dullness), promoting turnover, etc., and maintaining skin moisture, increasing flexibility, etc.
  • the anti-aging effect can be effectively and multifaceted.
  • the composition for external use of the present invention has an effect of increasing the moisture content of the stratum corneum and enhancing the softness and elasticity of the skin. Moreover, the composition for external use of this invention also has the effect
  • TEWL transepidermal water loss
  • the effect of improving the skin function can be expected by increasing the stratum corneum moisture content and increasing the lowered TEWL to keep the skin moisture content in an appropriate state. Can maintain skin. Therefore, the composition for external use of the present invention can also be used for the prevention / treatment of senile xeroderma.
  • the composition for external use of the present invention it is possible to prevent itching, eczema, pimples and the like by suppressing the drying of the skin and maintaining the transepidermal water loss (TEWL) appropriately.
  • TEWL transepidermal water loss
  • the balance between the stratum corneum moisture amount and the transepidermal water loss amount can be adjusted to an appropriate state, the skin state is kept normal, and it is refreshing. Can keep skin. Adjustment here means to lead to a healthy skin condition by improving the state where the TEWL of the skin is reduced and maintaining it when it is in an appropriate state.
  • the external composition for skin of the present invention contains the following essential oil (hereinafter sometimes referred to as component (A)) and purine base and / or a salt thereof (hereinafter sometimes referred to as component (B)). To do.
  • component (A) essential oil
  • component (B) purine base and / or a salt thereof
  • essential oil used as component (A) in the present invention contains volatile and lipophilic aromatic substances obtained from plant flowers, leaves, fruits, roots, bark, etc. It refers to an extract, and preferably refers to an extract containing a volatile and lipophilic fragrance obtained from a plant leaf, fruit, root, bark or the like.
  • the essential oil that can be used as the component (A) of the present invention is not particularly limited as long as the effect of the present invention is exhibited, and an essential oil obtained from each plant raw material can be used.
  • Dailicou (Illicium verum) oil Foeniculum vulgare oil, Pimpinella anisum oil, Thuja occidentalis Linn. Oil, Cedrus atlantica Manetti oil, Labandula Hybirda oil, rant oil Mentha arvensis var. Etc.
  • Daiwichi oil fennel oil, anise oil, scented oil, Atlas cedar oil, Labandula hybrida oil, lime oil, peppermint oil, pine oil, rosemary oil and turpentine oil
  • Daiki Oyster Oil Fennel Oil, Anise Oil, Akamatsu Oil, and Labandula Hybrida Oil
  • Daiki Oka Oil is particularly preferred.
  • one type may be selected from the above essential oils, or two or more types may be arbitrarily selected and used.
  • the mode of the combination is not particularly limited as long as the effect of the present invention is not impaired.
  • preferable combinations include, for example, Daiwichi oil, fennel oil, anise oil, eucalyptus oil, Atlas cedar oil, Labandula hybrida oil, lime from the viewpoint of effect and aroma.
  • a mixture of oil, mint oil, pine pine oil, rosemary oil and turpentine oil more preferably Daiwyo oil, scented oil, Atlas cedar oil, Labandula hybrida oil, lime oil, mint oil, pine pine oil, rosemary oil And a mixture of turpentine oils.
  • the effect of the present invention is more remarkably achieved by using such a mixture of essential oils or an essential oil containing a mixture as the component (A).
  • the parts of the various plant raw materials used when collecting the essential oil of the present invention are not particularly limited as long as a desired essential oil can be collected, and a part conventionally used according to the kind of plant is used. Can do.
  • plant parts such as flowers, stems, leaves, tree branches, fruits, roots and the like of various plants, and the above-ground parts of the plants, and more preferably plant parts such as stems, leaves, tree branches, fruits, roots, etc. of each plant. , And above-ground parts of plants.
  • an essential oil extracted from a fruit if it is a daikyo oil, a fennel oil and an anise oil.
  • odorant oil it is preferably an essential oil extracted from branches and leaves.
  • Atlas cedar oil it is preferably an essential oil extracted from the bark.
  • Lavandula hybrida oil it is preferably an essential oil extracted from whole grass.
  • lime oil it is preferably an essential oil extracted from fruits and peels.
  • mint oil it is preferably an essential oil extracted from whole grass.
  • pine oil it is preferably an essential oil extracted from leaves.
  • it is rosemary oil it is preferable that it is the essential oil extracted from the leaf.
  • turpentine oil it is preferably an essential oil extracted from Pinaceae trees.
  • the essential oil used in the present invention can be collected according to a conventionally known method, and examples of the collecting method include a steam distillation method, an oil adsorption method, a solvent extraction method, and a pressing method. These essential oil collection methods can be appropriately selected based on the type of plant raw material used, the extraction site, and the nature of the essential oil to be obtained. In addition, various essential oils sold as commercial products can be obtained and used more easily, for example, from Ogi Pharmaceutical Co., Ltd., Shiseido Pharmaceutical Co., Ltd. it can.
  • the blending ratio of the component (A) in the external composition of the present invention is not particularly limited as long as the effects of the present invention are exhibited.
  • the total amount of the component (A) is 0.00001% by weight or more, preferably 0.00001 to 40% by weight. More preferred is 0.0001 to 30% by weight, and still more preferred is 0.0001 to 25% by weight.
  • purine base and its salt As (B) component used in this invention, at least 1 sort (s) selected from the group which consists of a purine base and its salt is mentioned.
  • the purine base refers to various derivatives having purine or purine nucleus as a skeleton (hereinafter referred to as purine base).
  • the purine base used in the present invention is not particularly limited.
  • adenine, guanine, hypoxanthine, xanthine, adenosine, guanosine, inosine adenosine phosphate [adenosine 2′-monophosphate, adenosine 3 ′ Monophosphate, adenosine 5′-monophosphate (AMP), cyclic adenosine 3 ′, 5′-monophosphate (cAMP), adenosine 5′-diphosphate (ADP), adenosine 5′-triphosphate (ATP)], phosphate ester of guanosine (guanosine 3′-monophosphate, guanosine 5′-monophosphate, guanosine 5′-diphosphate, guanosine 5′-triphosphate), adenylosuccinic acid, xanthine acid, Inosinic acid, flavin a
  • adenosine monophosphate (adenosine 2′-monophosphate, adenosine 3′-monophosphate, AMP, cAMP) is preferable.
  • AMP when used in combination with the component (A), has a more prominent effect on promoting the secretion of IGF-1, increases the stratum corneum water content, and further maintains the transepidermal loss water content appropriately.
  • Preferred as the component (B) of the present invention Preferred as the component (B) of the present invention.
  • the purine base salt used in the present invention is not particularly limited.
  • salts of purine bases include salts with alkali metals such as sodium and potassium; alkaline earth metal salts such as calcium, magnesium and barium salts; salts with basic amino acids such as arginine and lysine; ammonium and tricyclohexyl Ammonium salts such as ammonium salts; salts with alkanolamines such as monoisopropanolamine, diisopropanolamine and triisopropanolamine; aliphatic dihydric alcohol derivatives such as aminomethylpropanol, aminomethylpropanediol and aminohydroxymethylpropanediol Can be mentioned. Of these, alkali metal salts are preferred.
  • the component (B) used in the present invention is preferably adenosine monophosphate monosodium or adenosine monophosphate disodium.
  • one type may be selected and used from the above component (B), or two or more types may be arbitrarily selected and used.
  • the mode of the combination is not particularly limited as long as the effect of the present invention is not impaired.
  • the blending ratio of the component (B) with respect to the total amount of the composition for external use of the present invention is, for example, 0.01% by weight or more, preferably 0.1 to 20% by weight, more preferably 0.1 to 10% by weight. Can be mentioned.
  • the component (B) is a salt of a purine base
  • the blending ratio is a value converted to the weight of the purine base.
  • composition for external use of the present invention is not particularly limited as long as it contains the components (A) and (B), and there is no limitation on the mode of combination thereof.
  • Component essential oil and (B) component: purine base and / or a salt thereof, for example, (A) component: Daiwichi oil, fennel oil, anise oil, scented oil, atlas seed (bark) oil, Laban Mixture of Dura hybrida oil, lime oil, peppermint oil, pine pine (leaf) oil, rosemary oil and turpentine oil and (B) component: adenosine phosphate ester or a salt thereof; (A) component: Daifenki oil, Essential oil obtained from at least one selected from the group consisting of fennel oil, anise oil, Scots pine oil and Labandula hybrida oil and component (B): a combination of AMP or a salt thereof ; (A) component: Daifyo oil, scented oil, Atlas cedar oil, Labandula hybrid
  • the mixing ratio of the component (A) and the component (B) in the external composition of the present invention is not particularly limited, and the mixing ratio of the components (A) and (B) described above, the form of the composition, and the expectation It can set suitably according to the effect etc. which are carried out.
  • the total amount of component (A) is 0.0000005 to 1000 parts by weight, preferably 0.000005 to 100 parts by weight, more preferably 0.000001 to 100 parts by weight, more preferably 1 part by weight of component (B)
  • the range which becomes 0.0001-100 weight part can be mentioned.
  • the component (B) is a salt of a purine base
  • the blending ratio is a value converted to the weight of the purine base.
  • composition for external use of the present invention is usually required to have a pH within a weakly acidic to neutral range, but is preferable from the viewpoint of hypoallergenicity to the skin and the effect of improving pigmentation. Is pH 5-7, more preferably pH 5.5-7.
  • a pH adjuster can be blended with the external preparation for skin.
  • the pH adjuster to be blended in this way is not particularly limited as long as it is weakly alkaline to alkaline and pharmaceutically or cosmetically acceptable. Examples include sodium hydroxide, L-arginine, aminomethylpropanediol, diisopropanolamine, triethanolamine and the like.
  • composition for external use of the present invention in addition to the above components, various components or additives usually added to the preparation for external use as necessary, for example, surfactant, solubilizing component, fats and oils, polyhydric alcohol, thickening Agents, preservatives, bactericides, moisturizers, colorants, dispersants, antioxidants, metal sequestering agents, skin astringents, whitening agents, pigments, deodorants and fragrances can be blended.
  • these components can be mix
  • the external composition of the present invention is not particularly limited as long as it is prepared as a composition to be applied to the skin in an external form.
  • the composition for external use of the present invention is blended with each of the above optional components as necessary, and further blended with other solvents and bases or carriers of commonly used external preparations as necessary, Prepare as external preparations in various desired forms such as paste, mousse, gel, liquid, emulsion, suspension, cream, ointment, sheet, stick, aerosol, spray, liniment, etc. be able to. These are prepared according to conventional methods in the art.
  • the use of the external composition of the present invention is not particularly limited.
  • the composition for external use of the present invention comprises: a skin external medicine; a skin external medicine; a makeup cosmetic such as a foundation, blusher, lip, mascara, eye shadow, eyeliner, white powder, sunscreen, emulsion, cream, Cosmetics such as basic cosmetics such as lotions, oils and packs; cleansing agents such as facial cleansers, cleansing and body cleaning agents; cleaning agents; detergents; bath preparations and other external preparations.
  • the external composition of the present invention is used by applying to human skin.
  • the amount and frequency of application of the external composition of the present invention For example, depending on the type / concentration of active ingredient, user's age, gender, symptom level, application form, expected level, etc. (Especially for pigmentation (stains); wrinkles); areas where skin dryness (such as elbows, knees, wrinkles, etc.); itching, eczema, pimples, etc. That's fine.
  • an application part will not be specifically limited, It can apply to the whole body.
  • the composition for external use of the present invention has an action of promoting IGF-1 secretion in the skin as shown in the test examples described below.
  • IGF-1 insulin-like growth factor
  • IGF-1 has a cell growth action in addition to an insulin-like effect (hypoglycemic action) and regulates cellular DNA synthesis. Therefore, by promoting the secretion of IGF-1 in the skin, the growth of skin cells is promoted, the diseases and symptoms of the skin epithelial layer are improved, and the healthy state of the skin is maintained.
  • the external composition of the present invention can be used as an external composition for promoting IGF-1 secretion or a composition for promoting production of IGF-1.
  • the composition for external use of the present invention can also be used as a composition for preventing skin aging, a composition for moisturizing, a composition for improving pigmentation, or a composition for whitening.
  • the composition for external use of the present invention has an action of increasing the moisture content of the stratum corneum and softening the stratum corneum. Therefore, the external composition of the present invention can be used as an external composition for increasing the stratum corneum moisture content in the skin.
  • the increase in the stratum corneum moisture content can be measured according to a conventionally known method.
  • a measuring instrument such as SKICON-200 (manufactured by IBI S Co., Ltd.) can be used. According to such a measuring instrument, it is possible to evaluate the change in the stratum corneum moisture content using the electric conductivity ( ⁇ S) as an index.
  • the composition for external use of the present invention has an action of appropriately maintaining the amount of transepidermal water loss.
  • the transepidermal water loss represents the amount of water transferred from the inside of the skin to the outside of the body, and by keeping this moderate, it is possible to suppress dryness of the skin and prevent itching, eczema, pimples and the like.
  • the composition for external use of the present invention in addition to the effect of increasing the stratum corneum moisture content, it has the effect of appropriately maintaining the transepidermal loss moisture content, so that the skin condition is kept normal, and the fresh skin Can be realized.
  • the composition for external use of the present invention when applied to skin having a reduced transepidermal water loss (TEWL), the TEWL can be increased and maintained in an appropriate state. Moreover, when TEWL is in an appropriate state, maintaining it can lead to a healthy skin state. Therefore, the external composition of the present invention can be used as an external composition for increasing the amount of transepidermal water loss or an external composition for adjusting the amount of transepidermal water loss.
  • the transepidermal water loss can be measured according to a conventionally known method. For example, a measuring instrument such as DermaLab (manufactured by Cortex Technology) can be used.
  • the external composition of the present invention can also be used as an external composition for providing an appropriate amount of transepidermal water loss while maintaining a high stratum corneum water content.
  • the composition for external use of this invention is useful for the function improvement of a stratum corneum based on such a function, and can keep a stratum corneum healthy.
  • the composition for external use of the present invention is useful for improving the symptoms of aging skin (specifically, rough skin surface, shallow cracks, itching, etc.) in which the stratum corneum moisture content and transepidermal water loss have been reduced. In particular, it can be effectively applied to the prevention / treatment of diseases (for example, senile xerosis) caused by the stratum corneum having reduced water retention ability and barrier function.
  • diseases for example, senile xerosis
  • the present invention provides a method for promoting IGF-1 secretion in the skin, which comprises applying the above components (A) and (B) to the skin. Furthermore, the present invention provides a method for preventing / treating xeroderma senile based on the improvement effect of the moisture retention function of the skin by promoting the secretion of IGF-1.
  • the application amount of each component in these methods can be appropriately set depending on the degree and range of symptoms, but is, for example, 1 to 5000 mg / day as the component (B) and divided into 2 to 3 times a day. It is preferable to apply.
  • the present invention also provides a method for easily producing an external composition having an IGF-1 secretion promoting action by blending the above components (A) and (B) with other components as necessary.
  • specific examples of each component, blending amounts, and the like are as described above.
  • compositions of Other Embodiments As shown in the Examples below, the present inventors have demonstrated that IGF-1 secretion can be achieved by using capsaicins together with purine bases and / or salts thereof (component (B)). I found that it was promoted. Therefore, the present invention also provides an external composition containing the component (B) and capsaicins. However, the capsaicins described here are not included in the essential oil and are distinguished from each other because they do not have the scent and volatility that are characteristic of the essential oil.
  • Capsaicins are known as hot pepper components, and include capsaicinoids (a general term for compounds in which a fatty acid is bonded to an acid amide in vanillylamine) and capsinoids (a general term for compounds in which a fatty acid is ester-bonded to vanillyl alcohol).
  • capsaicinoids include capsaicin ((6E) -N-[(4-Hydroxy-3-methoxyphenyl) methyl] -8-methylnon-6-enamide), non-anilic acid vanillylamide (N-Vanillylnonanamide) which is a synthetic capsaicinoid. It is done.
  • capsinoids include dihydrocapsiate.
  • capsaicin and synthetic capsaicinoid are preferable. Capsaicin can be extracted from chili pepper as a raw material according to a known method, but more conveniently can be obtained commercially from Tokyo Chemical Industry Co., Ltd.
  • the blending ratio of capsaicins with respect to the total amount of the composition for external use of the present invention is, for example, 0.000001% by weight or more, preferably 0.000001 to 0.01% by weight, and more preferably 0.000001 to 0.005% by weight.
  • the above purine base and / or salt thereof can be used.
  • the blending ratio of the component (B) and the capsaicins in the composition for external use of the present invention is not particularly limited as long as the effects of the present invention are exerted.
  • the capsaicins are 0.00000005 to 1 weight per 1 part by weight of the component (B). Parts, preferably 0.00000005 to 0.1 parts by weight, more preferably 0.0000001 to 0.1 parts by weight.
  • the component (B) is a salt of a purine base
  • the blending ratio is a value converted to the weight of the purine base.
  • composition for external use in the case of containing the component (B) and capsaicin
  • form and application method of the composition are described in “1. It is as described in the column of “External Composition”.
  • capsaicins are already known as IGF-1 secretion promoters
  • the present invention achieves higher IGF-1 secretion promotion than that using capsaicins alone by using capsaicins and purine bases in combination. It is possible.
  • the use concentration of capsaicins can be reduced.
  • Test Example 1 IGF-1 secretion promoting effect by combination of essential oil and AMP (1)
  • Test Example 1 400 ⁇ L of the test solution was applied to the back skin (3 cm ⁇ 5 cm) of a hairless mouse (Hos: HR-1, Nippon SLC Co., Ltd., female, 6-8 weeks old). After 30 minutes of application, the skin was collected, frozen and crushed, and the IGF-1 concentration in the skin was measured. Quantikine® Mouse IGF-1 Immunoassay (R & D Systems, Inc.) was used for the measurement of IGF-1 concentration.
  • test group was as shown in Table 2 below, and the composition shown in Table 1 was used as the test solution.
  • results are shown in FIG. 1a (mean value ⁇ standard error).
  • Test 1-2 Secreted IGF-1 concentration was measured according to the method described in Test 1-1.
  • the test groups were as shown in Table 3 below, and the compositions shown in Table 1 were used as test solutions.
  • the results are shown in FIG. 1b (mean value ⁇ standard error).
  • Test 1-3 Secreted IGF-1 concentration was measured according to the method described in Test 1-1.
  • the test groups were as shown in Table 4 below, and the compositions shown in Table 1 were used as test solutions. The results are shown in FIG. 1c (mean value ⁇ standard error).
  • AMP alone does not provide a sufficient IGF-1 secretion promoting effect, but in the compositions of Examples 1, 2 and 3, especially Examples 1 and 2, a remarkable secretion promoting action of IGF-1 It was shown to play.
  • Dai fennel oil contains anethole as a main component.
  • Anethole is also contained in fennel oil, anise oil, and the like, and therefore, even when fennel oil and anise oil are combined with AMP, excellent secretion promoting effect of IGF-1 is achieved as in the case of using daikyo oil. There is expected.
  • Test Example 2 IGF-1 Secretion Promoting Effect by Combination of Nonyl Acid Warinylamide and AMP
  • Example 1 shown in Table 1 above nonyl acid vanillylamide ((Tokyo Chemical Industry Co., Ltd.); concentration 0.001%) instead of essential oil
  • a test solution was prepared in the same manner as in Test Example 1, and this was designated as Reference Example 1.
  • the test liquid (Comparative Example 6) which does not contain nonylic acid valinylamide in Reference Example 1 and the test liquid (Comparative Example 7) which does not contain AMP in Reference Example 1 were used as controls.
  • Test Example 3 IGF-1 secretion promoting effect by the combination of essential oil and AMP (2) 300 ⁇ L of the test solution was applied to the back skin (3 cm ⁇ 5 cm) of a hairless mouse (Hos: HR-1, Nippon SLC Co., Ltd., female, 7 weeks old). After 30 minutes of application, the skin was collected, frozen and crushed, and the IGF-1 concentration in the skin was measured. Quantikine® Mouse IGF-1 Immunoassay (R & D Systems, Inc.) was used for the measurement of IGF-1 concentration.
  • test was a comparison between two groups with and without application.
  • other test oils (Atlas cedar oil) had a favorable aroma as a preparation. )
  • Essential oil mixture 0.03%
  • AMP 1% a suitable general base material.
  • Test Example 4 Effect on stratum corneum water content and transepidermal water loss (1)
  • 9 healthy men and ages 30 to 55 years were used as subjects.
  • a 5 ⁇ 8 cm region placed in front of the subject's left and right thighs was taken as the test site.
  • the test solution was applied to one of the left and right test sites, and the other test site was not applied.
  • the application amount is about 0.1g (2 drops of the used container) at a time, twice a day (AM / PM), and the application time is from 6:00 to 12:00.
  • the afternoon application was after bathing from 18:00 to 24:00.
  • skin milk having the composition shown in Table 7 below was used.
  • the subject washed the measurement site (thigh) with a designated soap (Kao White; manufactured by Kao Corporation), and then marked the measurement site with an oil-based pen.
  • a designated soap Kero White; manufactured by Kao Corporation
  • the patient was rested for 20 minutes on his / her back on the bed. Thereafter, the stratum corneum water content and transepidermal water loss were measured. At this time, the uncoated portion was used as a control.
  • the measurement was performed before the start of application, and after 4 weeks and 8 weeks after application. The results are shown in FIGS. 3a and 3b.
  • the measurement of the stratum corneum water content, the measurement of transepidermal water loss, and data analysis were performed according to the following methods.
  • ⁇ Corn layer moisture content> Using SKICON-200 (IBS Co., Ltd.), the electrical conductivity ( ⁇ S) was measured and used as an index of the stratum corneum moisture content. The measurement was carried out seven times, and the average value of the central five data was used as the measurement value.
  • Transepidermal water loss (TEWL)> Measure transepidermal water loss (g / h ⁇ m 2 ) using DermaLab (Cortex Technology). The measurement was performed 5 times, and the average value was taken as the measured value.
  • FIG. 3a From the results shown in FIG. 3a, it was shown that the stratum corneum water content increased significantly in 4 weeks and 8 weeks of application of the test solution. Moreover, FIG. 3b showed a significant increase in TEWL after 8 weeks of application of the composition for external use of the present invention, compared with no application.
  • Flexibility and elasticity are measured using a Cutometer MPA580 (CK electronic GmbH). Measurements were performed by standard methods described in the instructions that came with the instrument. The measurement was performed 5 times, and the average value was taken as the measured value.
  • the skin surface texture was evaluated by preparing a skin specimen sample.
  • the skin specimen sample was evaluated using a replica analysis system ASA-03R (Asahi Biomed) for reflection, creating a replica of the skin surface form by the method described in the attached manual, photographing the image.
  • ASA-03R Asahi Biomed
  • Test Example 4 From the results of Test Example 4, it is shown that the combination of the above 9 kinds of essential oils and AMP is applied to the skin to keep the skin moisture content normal and to improve the flexibility and elasticity. It was done. In addition, by applying the composition for external use of the present invention to the skin, the skin surface became finer, and fresh and healthy skin was obtained.
  • Test Example 5 Effect on stratum corneum water content and transepidermal water loss (2) In order to confirm that these effects were shown throughout the body, the following test was conducted. In this test example, 7 healthy men, age 39-57 years (average 49.0 years) were used as subjects. An area of 4 ⁇ 4 cm was placed on the left and right buttocks of the subject, and this was used as a test site. The test solution (cream formulation containing 0.5% AMP and 0.03% essential oil mixture) was applied to one of the left and right test sites, and the other test site was not applied. The application amount is about 0.2 g per application, twice a day (am / pm), and the application period is from 6:00 to 12:00 in the morning application and from 18:00 to 24 in the afternoon application period. After bathing until 0:00.
  • the test solution cream formulation containing 0.5% AMP and 0.03% essential oil mixture
  • Test Example 6 Effect on stratum corneum water content and transepidermal water loss (3)
  • five healthy men, ages 47 to 57 years (average 53.2 years) were used as subjects.
  • Two 4 ⁇ 4 cm regions were installed on the inner side of the left and right forearms of the subject, and these were used as test sites.
  • Apply the test liquid skin milk used in Test Example 3 above
  • commercially available general skin milk general preparation containing no adenosine monophosphate and essential oil in the other elbow side application part ) was applied.
  • the application frequency was twice a day (am / pm), and the application time zone was from 6:00 to 12:00 in the morning application and after bathing from 18:00 to 24:00 in the afternoon application.
  • the coating amount was about 0.05 g (one drop of the used container) at one time.
  • the subject washed the measurement site (inner forearm) with a designated soap (Kao White; manufactured by Kao Corporation), then marked the measurement site with an oil-based pen, temperature 20 ° C, relative humidity In a room controlled to 50% RH, the patient was rested for 20 minutes on his / her back on the bed. Thereafter, the stratum corneum water content and transepidermal water loss (TEWL) were measured. The measurement was performed before the start of application and 4 weeks after application.
  • a designated soap Kero White; manufactured by Kao Corporation
  • test solution skin lotion
  • general preparation skin lotion
  • test solution skin lotion
  • 2 is a graph showing the effects of essential oil (Daifenkou oil) and AMP on the amount of skin IGF-1 (in the figure, # represents P ⁇ 0.05).
  • 2 is a graph showing the effects of essential oil (Acacia pine oil) and AMP on the amount of skin IGF-1 (in the figure, # represents P ⁇ 0.05).
  • It is a graph which shows the effect

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EP18150042.2A EP3335693B1 (en) 2008-06-09 2009-04-22 Composition for external use
CN2009801009462A CN101854911B (zh) 2008-06-09 2009-04-22 外用组合物
EP09762333.4A EP2298275B1 (en) 2008-06-09 2009-04-22 Composition for external use
ES09762333.4T ES2671040T3 (es) 2008-06-09 2009-04-22 Composición para uso externo
US12/996,929 US10966983B2 (en) 2008-06-09 2009-04-22 Composition for external use
KR1020177003652A KR101850405B1 (ko) 2008-06-09 2009-04-22 외용 조성물
KR1020097026200A KR101746743B1 (ko) 2008-06-09 2009-04-22 외용 조성물
JP2009531683A JP4403467B1 (ja) 2008-06-09 2009-04-22 外用組成物
CA2727272A CA2727272A1 (en) 2008-06-09 2009-04-22 Composition for external use in suppressing dry skin

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JP2012188399A (ja) * 2011-03-11 2012-10-04 Kao Corp 皮膚保湿剤

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HK1179514A1 (en) 2013-10-04
KR101850405B1 (ko) 2018-04-19
JPWO2009150902A1 (ja) 2011-11-10
KR20100029741A (ko) 2010-03-17
EP3335693A1 (en) 2018-06-20
EP3335693B1 (en) 2023-09-13
US10966983B2 (en) 2021-04-06
JP5946234B2 (ja) 2016-07-05
TW200950815A (en) 2009-12-16
JP2010077130A (ja) 2010-04-08
ES2959848T3 (es) 2024-02-28
CN102885708A (zh) 2013-01-23
EP2298275A4 (en) 2013-12-18
EP2298275A1 (en) 2011-03-23
JP4403467B1 (ja) 2010-01-27
TW201417837A (zh) 2014-05-16

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